Elucidation of epigenome-mediated mechanism for growth supression in castration-resistant prostate cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21282
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology; Tumor biology
• Research Institution: Nagoya City University
• Principal Investigator: SATO Shinya 名古屋市立大学, 大学院医学研究科, 研究員 (30464564)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: HDAC阻害剤 / エピゲノム機構 / microRNA / アンドロゲン受容体 / ホルモン治療抵抗性前立腺癌 / heterogeneity / 網羅的増殖抑制メカニズム / 癌治療

Outline of Final Research Achievements

Targeting androgen receptor (AR) is one of the effective approaches for treatment of prostate cancers. Histone deacetylase (HDAC) alters the epigenetic status of tumor-associated genes, including those for miRNAs, and affects the behavior of cancers. We examined the molecular effects of a HDAC inhibitor, OBP-801, on prostate cancers. Treatment with OBP-801 efficiently suppressed cell growth of prostate cancer lines, together with AR downregulation, regardless of their hormone sensitivity. Among the upregulated miRNAs after OBP-801 treatment in the cell lines, miR-320a, was the most closely associated with AR expression. An miR-320a mimic suppressed AR protein expression together with growth suppression. Our data demonstrated that OBP-801 effectively suppressed AR activity via upregulation of miR-320a, which resulted in tumor cell growth suppression of prostate cancers. OBP-801 may be a promising AR-targeting reagent in AR-positive prostate cancer regardless of androgen dependency.

Free Research Field

腫瘍生物学